2-Cyanophenylboronic acid and its derivatives are effective as a raw material of a medicine and an electronic material such as liquid crystals used in the Suzuki coupling reaction.
Examples of common boronic acid production methods include: carrying out a transmetallation reaction between an aryl silane or an aryl stannane compound with boron tribromide, and then hydrolyzing the resulting product; coupling a halogenated aryl or an aryl triflate with pinacol borane or bispinacol diborate using a transition metal catalyst; and converting a halogenated aryl to an organic metal compound such as an aryl magnesium halide and aryl lithium, then reacting with trialkylborate.
While the latter method is commonly used as a method for producing industrially, even among boronic acids, since organic magnesium compounds react with a nitrile group, a method in which n-butyllithium and a halogenated benzonitrile are reacted at a low temperature is commonly used for cyanophenylboronic acids. In particular, 2-cyanophenylboronic acid can only be obtained at a low yield even if n-butyllithium is used. Patent Document 1 describes a method in which a subject compound is obtained in a good yield by reacting 2-bromobenzonitrile with a tertiary butyl lithium.
However, there are problems with this method, such as the fact that the raw materials, 2-bromobenzonitrile and tertiary butyl lithium, are expensive, and the fact that purity does not improve because byproducts which are difficult to separate, such as 2-cyano-3-bromophenylboronic acid, are produced. Another exemplary method is to obtain a pinacol ester of the subject cyanophenylboronic acid by coupling a halogenated benzonitrile with pinacol borane or bispinacol diborate using a noble metal catalyst. However, there are problems with this method as an industrial production method, in that the halogenated benzonitrile as a raw material and the pinacol borane raw material are expensive, and that an expensive catalyst is required for the coupling.
Non-patent Document 1 reports that a neopentyl glycol ester of 2-cyanophenylboronic acid can be obtained via an ortholithiation reaction by lithium 2,2,6,6-tetramethylpiperidide with benzonitrile as a raw material, then esterifying the resulting product with neopentyl glycol, and solidifying the resulting organic phase. However, in this method, the obtained neopentyl glycol ester of 2-cyanophenylboronic acid is mixed in a 3.5:1 proportion with N-benzoyl-2,2,6,6-tetramethylpiperidine. This method has the problem that, even though purification by recrystallization with a heptane solvent is carried out, once N-benzoyl-2,2,6,6-tetramethylpiperidine is introduced in the crystallization of the 2-cyanophenylboronic acid or in the subsequent esterification step, separation of the N-benzoyl-2,2,6,6-tetramethylpiperidine is difficult, so that the purity of the 2-cyanophenylboronic acid and its derivatives does not improve.    [Patent Document 1] European Patent EP-0675118A specification    [Non-patent Document 1] Organic Lett., 3(10), 1435 to 1437 (2001)